It has become evident that the microvasculature (i.e., the vasculature visible at the light microscopic level) plays a critical role in the plasticity of he brain under various physiological and pathological conditions, including fundamental processes in neuroplasticity such as axonal, dendritic and synaptic plasticity during brain development, learning, recovery from traumatic brain injury and brain inflammation, aging and neurodegeneration, as well as during neurogenesis (i.e., the generation of new neurons) and the migration of neuronal precursors (to their final destination in the brain). Accordingly, investigators have attempted for more than 30 years to trace, reconstruct, visualize and quantitatively characterize the microscopic three-dimensional (3D) micro-angioarchitecture of the brain in normal and pathological tissue (3D microangioarchitectonics). However, there has been very little use of 3D microangioarchitectonics in neuroscience research. This is due to the paucity of tools to study 3D microangioarchitectonics. We therefore propose to create Vesselucida, an innovative software product to perform advanced, interactive and automatic 3D microangioarchitectonics in normal and pathological brain tissue. This system will allow significant advancements in studies addressing the roles of microvessels on various aspects of neuroplasticity in neuroscience research, as well as in pharmacological and biotechnology research and development as the basis for the development of innovative treatments to fight complex brain diseases. Accordingly, the development of Vesselucida represents clear progress beyond the state-of-the-art, with great benefits for the neuroscience research community and society in general.